Increased circulating colony-stimulating factor-1 (CSF-1) in SJL/J mice
with radiation-induced acute myeloid leukemia (AML) is associated with
autocrine regulation of AML cells by CSF-1
N Haran-Ghera, R Krautghamer, T Lapidot, A Peled, MG Dominguez and ER Stanley
Department of Immunology, The Weizmann Institute of Science, Rehovot,
Israel.
The SJL/J mouse strain has a high spontaneous incidence of a B-cell
neoplasm, reticulum cell neoplasm type B (RCN B). In addition, following
irradiation, 10% to 30% of these mice develop acute myelomonocytic leukemia
(radiation-induced acute myeloid leukemia [RI- AML]), an incidence that can
be increased to 50% by treatment of the mice with corticosteroids after
irradiation. The role played by the mononuclear phagocyte growth factor,
colony-stimulating factor-1 (CSF- 1), in the development of RI-AML in SJL/J
mice was investigated. Mice dying of RI-AML, but not those dying of RCN B
or without disease, possessed elevated concentrations of circulating CSF-1.
In addition, in mice developing RI-AML with a more prolonged latency,
circulating CSF-1 concentrations were increased before overt expression of
RI-AML. First- passage tumors from 14 different RI-AMLs all contained high
concentrations of CSF-1, and six of six different first- or second- passage
tumors expressed the CSF-1 receptor (CSF-1 R). Furthermore, in vitro colony
formation by first- or second-passage tumor cells from 20 of 20 different
RI-AMLs was blocked by neutralizing anti-CSF-1 antibody, and four of four
of these tumors were inhibited by anti-CSF- 1R antibody. The results of
these antibody neutralization studies, coupled with the observation of
elevated circulating CSF-1 in mice developing RI-AML, show an autocrine
role for CSF-1 in RI-AML development in SJL/J mice. Southern blot analysis
of tumor DNA from six of six of these tumors failed to reveal any
rearrangements in the genes for CSF-1 or the CSF-1R. Studies in humans have
shown that patients with AML possess elevated levels of circulating CSF-1
and that AML cells can express CSF-1 and the CSF-1R. Thus, RI-AML in the
SJL/J mouse appears to be a useful model for human AML.
Volume 89,
Issue 7,
pp. 2537-2545,
04/01/1997
Copyright © 1997 by The American Society of Hematology
